A series of studies has been proposed with the long-range objective of defining the mechanisms involved in the regulation of somatomedin (SM) biosynthesis. The SM, insulin-like growth factor (IGF), released by cultured Buffalo rat liver (BRL) cells into serum-free medium, will be measured by a competitive protein binding, or radioligand, assay. Alterations in the hormonal and metabolic environment of the BRL cells will be studied to determine the influence of these factors on IGF synthesis/release. The incorporation of labeled amino acid precursors into IGF will be used to define its biosynthetic pathway and, in particular, to determine whether IGF is a cleavage product of a prohormone which might be releated to large molecular weight peptides in serum with insulin-like activity. If the biosynthesis of 3H-labeled IGF yields a product of sufficient purity and adequately high specific activity, it will be used as a probe to study the mechanism (s) of action of this SM on various target cells.